The present invention relates generally to methods and devices for delivery of a remote ischemic conditioning treatment. Such treatment may be used to achieve a variety of clinical benefits including for example a reduction of a harmful effect of ischemia and reperfusion injury of an organ, such as reducing of infarct size in a heart after acute myocardial infarction or reducing the extent of neuronal damage after a stroke. Other clinical benefits of remote ischemic conditioning may also be sought by using the devices and methods of the present invention—such as reducing inflammation, improving tissue survival, etc. as described in my previous patents as well as in related literature. More particularly, the invention describes methods and devices configured to deliver remote ischemic conditioning using partial limb occlusion.
The term “remote ischemic conditioning” is used herein to describe a non-invasive treatment generally consisting of a series of brief sub-lethal episodes of ischemia alternating with reperfusion applied to a limb of a subject (such as an upper arm or a thigh) in order to induce ischemic tolerance, reduce harmful effects of ischemia-reperfusion injury or to achieve other clinical benefits. Other terms used in the literature to describe this treatment include “remote ischemic postconditioning”, “remote ischemic perconditioning”, and “remote ischemic preconditioning”. For the purposes of this description, all such treatments are contemplated in this invention and are described using the general term “remote ischemic conditioning” whether the treatment is done prior to, during, or after the ischemia as well as prior to, during, or after restoration of blood flow to the ischemic organ or tissue bed.
An inflatable cuff placed over a limb of a subject may be conveniently used to deliver remote ischemic conditioning. Such cuffs are ubiquitously used for measurement of a subject's blood pressure or as pneumatic tourniquets and therefore are familiar not only to medical professionals but also to the general public.
U.S. Pat. No. 7,717,855 to Caldarone et al. is incorporated herein by reference in its entirety and discloses one example of an automatic device configured to deliver remote ischemic conditioning by periodic inflation and deflation of an inflatable cuff placed over a limb of a subject. Blood flow through the limb is entirely stopped for at least about one minute (and typically about 5 minutes) by inflating the cuff to a predetermined set pressure above the systolic blood pressure of the subject. One sited example of such set pressure is 200 mmHg. Upon deflation of the cuff, blood flow is restored to its unrestricted level for the entire duration of cuff deflation.
The approach described in the '855 patent has a limitation in that inflating the cuff to such high pressure for extended periods of time may cause pain and discomfort to the subject. In some subjects, prolonged cessation of blood flow may also cause clot formation and increase the risk of thromboembolism, especially when the limb of choice is a leg and not the upper arm.
There is a need therefore for a more gentle approach in delivering remote ischemic conditioning treatment aimed at achieving effective results at lower cuff inflation pressures and minimizing the risk of thrombus formation resulting from such treatment.